SpringerLink
Log in

Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-β1 and iNOS

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger (Zingiber officinale L.) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson’s trichrome staining. Transforming growth factor-beta 1 (TGF-β1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-α and IL-1β levels, MDA level, TGF-β1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-β1 and iNOS signaling pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

BLM:

Bleomycin

BALF:

Bronchoalveolar lavage fluid

GPx:

Glutathione peroxidase

eNOS:

Endothelial nitric oxide synthase

EMT:

Epithelial-mesenchymal transition

ECM:

Extracellular matrix

HxE:

Hematoxylin-Eosin

HMGB1:

High mobility group box 1 protein

IPF:

Idiopathic pulmonary fibrosis

IHC:

Immunohistochemical

iNOS:

Inducible nitric oxide synthase

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

MDA:

Malondialdehyde

nNOS:

Neuronal nitric oxide synthase

NO:

Nitric oxide

NF-κB:

Nuclear factor-κB

PF:

Pulmonary fibrosis

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TBARS:

Thiobarbituric acid reactive substances

TGF-β1:

Transforming growth factor-beta 1

TNF-α:

Tumor necrosis factor alpha

References

  • Ahmad B, Rehman MU, Amin I, Mir MUR, Ahmad SB, Farooq A, Muzamil S, Hussain I, Masoodi M, Fatima B (2018) Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) protects against alloxan-induced diabetes via alleviation of oxidative stress and inflammation: probable role of NF-kB activation. Saudi Pharm J 26(8):1137–1145

    PubMed  PubMed Central  Google Scholar 

  • Alam MF (2018) Neuro-protective effects of zingerone against carbontetrachloride (CCl4) in-duced brain mitochondrial toxicity in Swiss albino mice. J Appl Nat Sci 10(2):548–552

    CAS  Google Scholar 

  • Ali BH, Blunden G, Tanira MO, Nemmar A (2008) Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 46(2):409–420

    CAS  PubMed  Google Scholar 

  • Aristoteles LR, Righetti RF, Pinheiro NM, Franco RB, Starling CM, da Silva JC, Pigati PA, Caperuto LC, Prado CM, Dolhnikoff M, Martins MA, Leick EA, Tibério IF (2013) Modulation of the oscillatorymechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model. BMC Pulm Med 13(1):52

    PubMed  PubMed Central  Google Scholar 

  • Chakraborty K, Dey A, Bhattacharyya A, Dasgupta SC (2019) Anti-fibrotic effect of black tea (Camellia sinensis) extract in experimental pulmonary fibrosis. Tissue Cell 56:14–22

    CAS  PubMed  Google Scholar 

  • Chen J, Lu J, Wang B, Zhang X, Huang Q, Yuan J, Hao H, Chen X, Zhi J, Zhao L, Chu H (2018) Polysaccharides from Dendrobium officinale inhibit bleomycin-induced pulmonary fibrosis via the TGFβ1-Smad2/3 axis. Int J Biol Macromol 118:2163–2175

    CAS  PubMed  Google Scholar 

  • Cheong KO, Shin DS, Bak J, Lee C, Kim KW, Je NK, Chung HY, Yoon S, Moon JO (2016) Hepatoprotective effects of zingerone on carbon tetrachlorideand dimethylnitrosamine-induced liver injuries in rats. Arch Pharm Res 39:279–291

    CAS  PubMed  Google Scholar 

  • Choi JS, Ryu J, Bae WY, Park A, Nam S, Kim JE, Jeong JW (2018) Zingerone suppresses tumor development through decreasing cyclin D1 expression and inducing mitotic arrest. Int J Mol Sci 19(9):E2832

    PubMed  Google Scholar 

  • Degryse AL, Tanjore H, Xu XC, Polosukhin VV, Jones BR, McMahon FB, Gleaves LA, Blackwell TS, Lawson WE (2010) Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis. Am J Phys Lung Cell Mol Phys 299(4):L442–L452

    CAS  Google Scholar 

  • Della Latta V, Cecchettini A, Del Ry S, Morales MA (2015) Bleomycin in the setting of lung fibrosis induction: from biological mechanisms to counteractions. Pharmacol Res 97:122–130

    CAS  PubMed  Google Scholar 

  • Di Paola R, Talero E, Galuppo M, Mazzon E, Bramanti P, Motilva V, Cuzzocrea S (2011) Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis. Respir Res 8(12):41

    Google Scholar 

  • El-Bassossy HM, Al-Thubiani WS, Elberry AA, Mujallid MI, Ghareib SA, Azhar AS, Banjar ZM, Watson ML (2017) Zingerone alleviates the delayed ventricular repolarization and AV conduction in diabetes: effect on cardiac fibrosis and inflammation. PLoS One 12(12):e0189074

    PubMed  PubMed Central  Google Scholar 

  • Förstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33(7):829–837

    Google Scholar 

  • Gharaee-Kermani M, Ullenbruch M, Phan SH (2015) Animal models of pulmonary fibrosis. Methods Mol Med 117:251–259

    Google Scholar 

  • Gow AJ, Ischiropoulos H (2001) Nitric oxide chemistry and cellular signaling. J Cell Physiol 187:277–282

    CAS  PubMed  Google Scholar 

  • Guo C, Atochina-Vasserman E, Abramova H, George B, Manoj V, Scott P, Gow A (2016) Role of NOS2 in pulmonary injury and repair in response to bleomycin. Free Radic Biol Med 91:293–301

    CAS  PubMed  Google Scholar 

  • Ho CY, Lu CC, Jhang JJ, Yen GC (2017) Diallyl sulfide attenuates transforming growth factor-β-stimulated pulmonary fibrosis through Nrf2 activation in lung MC-5 fibroblast. J Funct Foods 28:31320

    Google Scholar 

  • Hsiang CY, Cheng HM, Lo HY, Li CC, Chou PC, Lee YC, Ho TY (2015) Ginger and zingerone ameliorate lipopolysaccharide-induced acute systemic inflammation in mice, assessed by nuclear factor-κB bioluminescent imaging. J Agric Food Chem 63(26):6051–6058

    CAS  PubMed  Google Scholar 

  • Izbicki G, Segel MJ, Christensen TG, Conner MW, Breuer R (2002) Time course of bleomycin-induced lung fibrosis. Int J Exp Pathol 8(3):111–119

    Google Scholar 

  • Jakowlew SB, Mariano J (2003) Detection of the transcripts and proteins for the transforming growth factor-beta isoforms and receptors in mouse lung tumorigenesis using in situ hybridization and immunohistochemistry in paraffin-embedded tissue sections. Methods Mol Med 74:145–166

    CAS  PubMed  Google Scholar 

  • Ji Y, Dou YN, Zhao QW, Zhang JZ, Yang Y, Wang T, **a YF, Dai Y, Wei ZF (2016) Paeoniflorin suppresses TGF-β mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway. Acta Pharmacol Sin 37(6):794–804

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kalayarasan S, Sriram N, Sudhandiran G (2008) Diallyl sulfide attenuates bleomycin-induced pulmonary fibrosis: critical role of iNOS, NF-kappaB, TNF-alpha and IL-1beta. Life Sci 6(8):1142–1153

    Google Scholar 

  • Kanter M, Sahin SH, Basaran UN, Ayvaz S, Aksu B, Erboga M, Colak A (2004) The effect of methylene blue treatment on aspiration pneumonia. J Surg Res 193:909–919

    Google Scholar 

  • Kaygusuzoglu E, Caglayan C, Kandemir FM, Yıldırım S, Kucukler S, Kılınc MA, Saglam YS (2018) Zingerone ameliorates cisplatin-induced ovarian and uterine toxicity via suppression of sex hormone imbalances, oxidative stress, inflammation and apoptosis in female Wistar rats. Biomed Pharmacother 102:517–530

    CAS  PubMed  Google Scholar 

  • Kim MK, Chung SW, Kim DH, Kim JM, Lee EK, Kim JY, Ha YM, Kim YH, No JK, Chung HS, Park KY, Rhee SH, Choi JS, Yu BP, Yokozawa T, Kim YJ, Chung HY (2010) Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway. Exp Gerontol 45(6):419–426

    CAS  PubMed  Google Scholar 

  • King TE Jr, Pardo A, Selman M (2011) Idiopathic pulmonary fibrosis. Lancet 378:1949–1961

    PubMed  Google Scholar 

  • King GG, James A, Harkness L, Wark PAB (2018) Pathophysiology of severe asthma: we’ve only just started. Respirology 23(3):262–271

    PubMed  Google Scholar 

  • Kolb M, Vašáková M (2019) The natural history of progressive fibrosing interstitial lung diseases. Respir Res 20(1):57

    PubMed  PubMed Central  Google Scholar 

  • Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J (2001) Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest 107:1529–1536

    CAS  PubMed  PubMed Central  Google Scholar 

  • Labib RM, Youssef FS, Ashour ML, Abdel-Daim MM, Ross SA (2017) Chemical composition of Pinus roxburghii bark volatile oil and validation of its anti-inflammatory activity using molecular modelling and bleomycin-induced inflammation in albino mice. Molecules 22(9):E1384

    PubMed  Google Scholar 

  • Lakari E, Soini Y, Säily M, Koistinen P, Pääkkö P, Kinnula VL (2002) Inducible nitric oxide synthase, but not xanthine oxidase, is highly expressed in interstitial pneumonias and granulomatous diseases of human lung. Am J Clin Pathol 117(1):132–142

    CAS  PubMed  Google Scholar 

  • Lappalainen U, Whitsett JA, Wert SE, Tichelaar JW, Bry K (2005) Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am J Respir Cell Mol Biol 32:311–318

    CAS  PubMed  Google Scholar 

  • Lee W, Ku SK, Bae JS (2017) Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice. Toxicol Appl Pharmacol 329:202–211

    CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  • Lucarini L, Durante M, Lanzi C, Pini A, Boccalini G, Calosi L, Moroni F, Masini E, Mannaioni G (2017) HYDAMTIQ, a selective PARP-1 inhibitor, improves bleomycin-induced lung fibrosis by dampening the TGF-b/SMAD signalling pathway. J Cell Mol Med 21(2):324–335

    CAS  PubMed  Google Scholar 

  • Mani V, Arivalagan S, Islam Siddique A, Namasivayam N (2017) Antihyperlipidemic and antiapoptotic potential of zingerone on alcohol induced hepatotoxicity in experimental rats. Chem Biol Interact 272:197–206

    CAS  PubMed  Google Scholar 

  • Mansouri MT, Vardanjani HR, Hemmati AA, Tabandeh MR, Rezaie A, Pashmforosh M, Angali KA (2019) Zingerone attenuates bleomycin-induced pulmonary fibrosis in rats. Jundishapur J Nat Pharm Prod 14(1):e80098

    CAS  Google Scholar 

  • Meng Y, Zhang X, Wang H, Dong H, Gu X, Yu X, Liu Y (2019) Yangyin Yiqi mixture ameliorates bleomycin-induced pulmonary fibrosis in rats through inhibiting TGF-훽1/Smad pathway and epithelial to mesenchymal transition. Evid Based Complement Alternat Med 2019:2710509–2710513. https://doi.org/10.1155/2019/2710509

    Article  PubMed  PubMed Central  Google Scholar 

  • Miyazawa H, Takiguchi Y, Hiroshima K, Kurosu K, Tada Y, Kasahara Y, Sakao S, Tanabe N, Tatsumi K, Kuriyama T (2008) Pulmonary and systemic toxicity of bleomycin on severe combined immune deficiency mice. Exp Lung Res 34(1):1–17

    CAS  PubMed  Google Scholar 

  • Mohammed ET, Hashem KS, Ahmed AE, Aly MT, Aleya L, Abdel-Daim MM (2020) Ginger extract ameliorates bisphenol A (BPA)-induced disruption in thyroid hormones synthesis and metabolism: involvement of Nrf-2/HO-1 pathway. Sci Total Environ 703:134664

    CAS  PubMed  Google Scholar 

  • Morishima Y, Nomura A, Uchida Y, Noguchi Y, Sakamoto T, Ishii Y, Goto Y, Masuyama K, Zhang MJ, Hirano K, Mochizuki M, Ohtsuka M, Sekizawa K (2001) Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding. Am J Respir Cell Mol Biol 24:1–11

    CAS  PubMed  Google Scholar 

  • Mouratis MA, Aidinis V (2011) Modeling pulmonary fibrosis with bleomycin. Curr Opin Pulm Med 17(5):355–361

    CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

    CAS  PubMed  Google Scholar 

  • Pini A, Viappiani S, Bolla M, Masini E, Bani D (2012) Prevention of bleomycin-induced lung fibrosis in mice by a novel approach of parallel inhibition of cyclooxygenase and nitric-oxide donation using NCX 466, a prototype cyclooxygenase inhibitor and nitric-oxide donor. J Pharmacol Exp Ther 341:493–499

    CAS  PubMed  Google Scholar 

  • Possa SS, Leick EA, Prado CM, Martins MA, Tib’erio IFLC (2013) Eosinophilic inflammation in allergic asthma. Front Pharmacol 17(4):46

    Google Scholar 

  • Prado CM, Martins MA, Tib’erio IF (2011) Nitric oxide in asthma physiopathology. ISRN Allergy 2011:832560

    PubMed  PubMed Central  Google Scholar 

  • Prasad R, Gupta N, Singh A, Gupta P (2015) Diagnosis of idiopathic pulmonary fibrosis: current issues. Intractable Rare Dis Res 4(2):65–69

    PubMed  PubMed Central  Google Scholar 

  • Rao BN, Rao BS (2010) Antagonistic effects of zingerone, a phenolic alkanone against radiation-induced cytotoxicity, genotoxicity, apoptosis and oxidative stress in Chinese hamster lung fibroblast cells growing in vitro. Mutagenesis 25(6):577–587

    CAS  PubMed  Google Scholar 

  • Ricciardolo FL, Sterk PJ, Gaston B, Folkerts G (2004) Nitric oxide in health and disease of the respiratory system. Physiol Rev 84(3):731–765

    CAS  PubMed  Google Scholar 

  • Ruscitti F, Ravanetti F, Essers J, Ridwan Y, Belenkov S, Vos W, Ferreira F, KleinJan A, van Heijningen P, Van Holsbeke C, Cacchioli A, Villetti G, Stellari FF (2017) Longitudinal assessment of bleomycin-induced lung fibrosis by micro-CT correlates with histological evaluation in mice. Multidiscip Respir Med 10(12):8

    Google Scholar 

  • Semwal RB, Semwal DK, Combrinck S, Viljoen AM (2015) Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry 117:554–568

    CAS  PubMed  Google Scholar 

  • Sener G, Topaloğlu N, Sehirli AO, Ercan F, Gedik N (2007) Resveratrol alleviates bleomycin-induced lung injury in rats. Pulm Pharmacol Ther 20(6):642–649

    CAS  PubMed  Google Scholar 

  • Shariati S, Kalantar H, Pashmforoosh M, Mansouri E, Khodayar MJ (2019) Epicatechin protective effects on bleomycin-induced pulmonary oxidative stress and fibrosis in mice. Biomed Pharmacother 114:108776

    CAS  PubMed  Google Scholar 

  • Sogut S, Ozyurt H, Armutcu F, Kart L, Iraz M, Akyol O, Ozen S, Kaplan S, Temel I, Yildirim (2004) Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats. Eur J Pharmacol 494:213–220

    CAS  PubMed  Google Scholar 

  • Soliman AF, Anees LM, Ibrahim DM (2018) Cardioprotective effect of zingerone against oxidative stress, inflammation, and apoptosis induced by cisplatin or gama radiation in rats. Naunyn Schmiedebergs Arch Pharmacol 391(8):819–832

  • Sriram N, Kalayarasan S, Sudhandiran G (2009) Epigallocatechin-3-gallate augments antioxidant activities and inhibits inflammation during bleomycin-induced experimental pulmonary fibrosis through Nrf2-Keap1 signaling. Pulm Pharmacol Ther 22(3):221–236

    CAS  PubMed  Google Scholar 

  • Theodoro-Júnior OA, Righetti RF, Almeida-Reis R, Martins-Oliveira BT, Oliva LV, Prado CM, Saraiva-Romanholo BM, Leick EA, Pinheiro NM, Lobo YA, Martins MA, Oliva ML, Tibério IF (2017) A plant proteinase inhibitor from enterolobium contortisiliquum attenuates pulmonary mechanics, inflammation and remodeling induced by elastase in mice. Int J Mol Sci 18(2):E403

    PubMed  Google Scholar 

  • Turgut NH, Kara H, Elagoz S, Deveci K, Gungor H, Arslanbas E (2016) The protective effect of naringin against bleomycin-induced pulmonary fibrosis in Wistar rats. Pulm Med 2016:7601393

    PubMed  PubMed Central  Google Scholar 

  • Williamson JD, Sadofsky LR, Hart SP (2015) The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis. Exp Lung Res 41(2):57–73

    CAS  PubMed  Google Scholar 

  • Wolters PJ, Collard HR, Jones KD (2014) Pathogenesis of idiopathic pulmonary fibrosis. Annu Rav Pathol 9:157–179

    CAS  Google Scholar 

  • **e X, Sun S, Zhong W, Soromou LW, Zhou X, Wei M, Ren Y, Ding Y (2014) Zingerone attenuates lipopolysaccharide-induced acute lung injury in mice. Int Immunopharmacol 19(1):103–109

    CAS  PubMed  Google Scholar 

  • Yeung AWK, Tzvetkov NT, El-Tawil OS, Bungǎu SG, Abdel-Daim MM, Atanasov AG (2019) Antioxidants: scientific literature landscape analysis. Oxidative Med Cell Longev 2019:8278454

    Google Scholar 

  • Zaafan MA, Haridy AR, Abdelhamid AM (2019) Amitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2. Naunyn Schmiedeberg's Arch Pharmacol 392(3):279–286

    CAS  Google Scholar 

Download references

Funding

This study was financially supported by the Cumhuriyet University Scientific Research Project V-070 (CUBAP, Sivas, Turkey).

Author information

Author notes

  1. Emre Arslanbas

    Present address: Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum, Turkey

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Cumhuriyet University, 58140, Sivas, Turkey

    Huseyin Gungor, Haki Kara & Emre Arslanbas

  2. Department of Physiology, Faculty of Veterinary Medicine, Cumhuriyet University, 58140, Sivas, Turkey

    Mehmet Ekici

  3. Department of Pathology, Faculty of Veterinary Medicine, Cumhuriyet University, 58140, Sivas, Turkey

    Mehmet Onder Karayigit

  4. Department of Pharmacology, Faculty of Pharmacy, Izmir Katip Celebi University, 35620, Izmir, Turkey

    Nergiz Hacer Turgut

Authors
  1. Huseyin Gungor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mehmet Ekici
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehmet Onder Karayigit
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nergiz Hacer Turgut
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haki Kara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emre Arslanbas
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HG and NHT designed research. HG, ME and MOK conducted experiments. HG, HK and EA analyzed the data. NHT wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Nergiz Hacer Turgut.

Ethics declarations

The experimental protocol was approved by the Sivas Ethical Committee for Animal Experiments (HADYEK) (Number: 65202830-050.04.04-129) and all experiments were conducted in accordance with EU Directive 2010/63/EU for animal experiments.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gungor, H., Ekici, M., Onder Karayigit, M. et al. Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-β1 and iNOS. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1659–1670 (2020). https://doi.org/10.1007/s00210-020-01881-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-020-01881-7

Keywords

Search

Navigation